Tumor angiogenesis is a complex process in which new blood vessels are formed in response to interactions between tumor cells and endothelial cells (ECs), growth factors, and extracellular matrix components. Tumor vessels promote growth and progression of human solid tumors (e.g., cancer of the liver, bladder, and prostate). New tumor blood vessels penetrate into cancerous growths, supplying nutrients and oxygen and removing waste products (Jung et al., 2002; Folk-man, 2002; Kerbel and Kamen, 2004; Stupack and Cheresh, 2004). A large number of studies have demonstrated that tumor cells secrete angiogenic growth factors to stimulate EC proliferation and to induce angiogenesis. Among them, vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors, and it is overexpressed in many human cancers (Jung et al., 2002).
Targeting VEGF for human cancer therapy has shown some promise in the treatment of colorectal cancer, demonstrating the potential for cancer therapy based upon blocking angiogenesis (Ferrara et al., 2004). However, targeting VEGF for human cancer therapy has not been successful in a multiplicity of other tumor types, suggesting that other factors or components also play a critical role in tumor angiogenesis (Jung et al., 2002; Kerbel and Kamen, 2004). The identification of these factors and components have important implications in human cancer therapy.
Thus, there is need for the identification of other factors or components that are involved in tumor angiogenesis. Furthermore, new compositions and methods are required to target these factors that can be used to treat cancer (e.g., to inhibit angiogenesis, whose loss is associated with cancer).